Preparation of beta-alanine



Patented Nov 30, 1943 rnnmnarron or BETA-ALANINE Russell 1 Dean, Stami'ord, com, assignor to American Cyanamid Company,

New York,

Y., a corporation of Maine No Drawing.

13 Claims.

This invention relates to the preparation of beta-aminopropionic acid (beta-alanine) and more particularly, to the preparation of' betaaminopropionic acid in one step from dihydracrylonitrile and ammonium hydroxide or from thiodihydracrylonitrileand ammonium hydroxide. 7

According to the present invention I have found that compounds represented by the formula cH}cHcN X CHzCHrCN wherein X stands for oxygen or sulfur, and ammonium hydroxide, when heated together in a practicable method of preparing this intermediate is indicated. The process of the present invention provides such a method.

It is an advantage of the present invention that the only reactants essential for the operation of the process are dihydracrylonitrile or thiodihydracrylonitrile and ammonium hydroxide, all of which are readily available.

It is another advantage of the present invention that the reaction involved is simple, easily controlled, and takes place in a .single step. Thus, beta-aminopropionic acid may be produced directly from dihydracrylonitrile. or thiodihydracrylonitrile without requiring the isolation of any intermediate product.

It is, a further advantage of the invention that the beta-aminopropionic acid is obtained in good yield in a form which permits easy separation from the reaction mixture.

The invention will be described in greater detail in conjunction with the following specific examples. It should be understood that these examples are merely specific embodiments of the invention and it is not intended to limit the scope of the invention to the specific details therein set forth; Parts are by weight unless otherwise stated. Example. 1

272 parts (2.19 mols) of dihydracrylonitrile, 26 parts of 28% ammonium hydroxide, and 702 parts Application June 25, 1942, Serial No. 448,490

. of water were heated in an autoclave at 180-200 ume under reduced pressure.

C. for four and a half hours. The solution was cooled, clarified, and concentrated to small vol- 1 1. of dry methanol was added, the mixture was stirred to effect complete solution, and then cooled. Forty-seven parts of beta-aminopropionic acid crystallized out. Yield: 12%.

Example 2 After recovery of the beta-aminopropionic acid as described in Example 1, the filtrate was evaporated to reclaim the methanol. The resulting syrupy residue was heated with an additional amount of ammonium hydroxide at 200 C. for

- four hours and the solution treated as described Example 3 200 parts of thiodihydracrylonitrile, 600 parts of 28% ammonium hydroxide, 1080 parts of water and 2 parts of diphenylamine were heated to 200 C; for four hours in an autoclave. The solution was filtered, treated with decolorizing carbon at 0., again filtered, and the filtrate evaporated to a thick syrup. The syrup was then diluted with 500 mls. of methanol, whereupon 59 parts of beta-aminopropionic acid suitable for the production of pantothenic acid without further purification crystallized out. Yield: 24%.

Apparently an equilibrium is reached in the reaction between dihydracryl'onitrile or thiodihydracrylonitrile and ammonium hydroxide which may account for the fact that the residue from one operation may be used as the reactant in another with no appreciable decrease in the yield oi beta-aminopropionic acid obtained. When over-all yields are considered, this feature of my process is extremely important since yields approaching the theoretical may be obtained by reworking the residues.

Further evidence for the existence of an equilibrium mixture was obtained from a series of further reactions wherein concentrations of the reactants, time of heating and temperature were varied within wide limits. The strength of the ammonium hydroxide was varied from 2% to 28% with similar variations in the proportion of the dihydracrylonitriles based on the proportion 4 to 250 C. In all cases beta-aminopropionic acid was obtained but only drastic changes in the concentration of reactants gave more than a 35% yield. For example, very low concentrations of and isolated in this form.

the 'dihydracrylonitriles produced beta-aminopropioiiic acid in yields of the order of 50%60% but the increased cost of removing the larger volumes of solvent present would probably neutralize the economical advantages resulting from the increased yields. 7

The beta-aminopropionic acid produced by my process may, ifdesired, be converted to an acid salt such as the hydrochloride or to a salt of a metal such as an alkali or alkaline earth metal, I prefer, however, to isolate the beta-aminopropionic acid directly from the concentrated syrupy reaction product by diluting it with absolute methanol. When so isolated, the beta-aminopropionic acid is in a pure form and may then, if desired, be converted to the salts when they are required as intermediates in processes for producing pantothenic acid.

Methanol appears to be peculiarly suited for the above isolation or crystallization step. Attempts to dilute with various other aliphatic alcohols such as ethanol or propanol have been unsatisfactory.

In the reaction between dihydracrylonitrile or thiodihydracrylonitrile and ammonium hydroxide under the conditions described above, it may be desirable in some instances to add other substances to the reaction mixture. For example, dehydration catalyst, ammonium salts of weak acids such as ammonium carbonate, inhibitors, anti-oxidants, and other suitable reagents for slightly altering the course or speed of the reaction may be added.

I claim:

1. The process of producing beta-aminopropionic acid which comprises reacting a substance of the group consisting of dihydracrylonitrile and thiodihydracrylonitrile with aqueous ammonia at an elevated temperature.

2. The process of producing beta-aminopropionic acid which comprises reacting a substance of the group consisting of dihydracrylonitrile and thiodihydracrylonitrile with aqueous ammonia at a temperature of from about 180 C. to about 225 C.

3. The process of producing beta-aminopropicnic acid which comprises reacting a substance of the group consisting of dihydracrylonitrile and thiodihydracrylonitrile with aqueous ammonia at a temperature of about 200 C. for from about one to about twenty-four hours.

4. The process of producing beta-aminopropicnic acid which comprises heating dihydracrylonitrile and aqueous ammonia at a temperature of about 200 C. for about four hours.

5,. The process of producing beta-aminopropicnic acid which comprises heating thiodihydracrylonitrile and aqueous ammonia at a temperature of about 200 C. for about four hours.

6. The process of producing beta-aminopropionic acid which comprises reacting a substance of the group consisting of dihydracrylonitrile and thiodihydracrylonitrile with aqueous ammonia at a temperature of from about 180 C. to about 225 C. for from about one to about twentyfour hours, concentrating the reaction mixture to a syrup, and diluting the syrup with methanol to cause precipitation of beta-aminopropionic acid.

7. The process of'producing beta-aminopropicnic acid which comprises reacting dihydracrylonitrile with aqueous ammonia at a temperature of about 200 C. for about four hours, concentrating the reaction mixture to a syrup, and

diluting the syrup with methanol to cause precipitation of beta-aminopropionic acid.

3. The process of producing beta-aminopropicnic acid which comprises reacting dihydra- 10 crylonitrile with aqueous ammonia at a temperature of about 200 C. for about four hours, concentrating the reaction mixture to a syrup and diluting the syrup with methanol to cause precipitation of beta-aminopropionic acid.

9. The process according to claim 1 in which the residue produced is reacted with a fresh quantity of aqueous ammonia at an elevated temperature to produce a further quantity of beta-aminopropionic acid.

10. The process of producing beta-aminopropicnic acid which comprises reacting dihydracrylonitrile with aqueous ammonia at a temperature of from about 180 C. to about 225 C. for from about one to about twenty-four hours, concentrating the reaction mixture to a syrup, diluting the syrup with methanol, collecting the precipitated beta-aminopropionic acid, concentrating the residue, and reacting said residue with aqueous ammonia at a temperature of from 0 about 180 C. to about 225 C. for from about one to about twenty-four hours to produce a further quantity of beta-aminopropionic acid.

11. The process of producing beta-aminopropionic acid which comprises reacting thiodihydracrylonitrile with aqueous ammonia at a temperature of from about 180 C. to about 225 C. for from about one to about twenty-four hours, concentrating the reaction mixture to a syrup, diluting the syrup with methanol, collecting the precipitated beta-aminopropionic acid, concentrating the residue, and reacting said residue with aqueous ammonia at a temperature of fromabout 180 C. to about 225 C. for from about one to about twenty-four hours to produce a further quantity of beta-aminopropionic acid.

12. The process of producing beta-aminopropionic acid which comprises heating at a ternperature of about 200 C. a mixture of dihydracrylonitrile and aqueous ammonia for about four hours, concentrating the reaction mixture to a, syrup, diluting the syrup with methanol, collecting the precipitated beta-aminopropionic acid, concentrating the residue, and reacting said residue with aqueous ammonia at about 200 C.

for about four hours, to produce a further quantity of beta-aminopropionic acid.

13. The process of producing beta-aminopro= picnic acid which comprises heating at a temperature of about 200 C. a mixture of dihydracrylonitrile and aqueous ammonia for about four hours, concentrating the reaction mixture to a syrup, diluting the syrup with methanol, collecting the precipitated beta-aminopropionic acid, concentrating the residue, and reacting said residue with aqueous ammonia at about 200 C. for about four hours to produce a further quantity of beta-aminopropionic acid.

RUSSELL T. DEAN. 

